Background and aims: Leucine, Isoleucine, and Valine collectively known as Branchedchain amino acids (BCAAs), can be closely associated with metabolic dysregulates and with insulin resistance. We aimed to explore the role of BCAAs as potential treatment option for diabetes. Material and method: Bioassay the effect of BCAAs on MIN6 cell line on insulin secretion and pancreatic beta cells expansion, then were checked for inhibitory potential of pancreatic amylase, glucosidase and lipase as alternative approach for diabetes treatment. Results: BCAAs significantly enhance insulin secretion parallel to L-alanine efficacy. Furthermore, BCAAs obtain a dose dependent β-cell proliferation similar to glucagon-like peptide-1. Moreover, these acids could restore the secretory function of MIN6 β-cell despite stressful gluco-lipo-toxicity; separately or combined. Moreover, BCAAs exerted a dose dependent dual inhibition of amylase, glucosidase and lipase. Conclusions: Our current findings suggest that BCAAs supplementation may have a potential therapeutic effect against diabetes as insulin releasing agent and as specific inhibitors for both -amylase/α-amyloglucoside and lipase key words: BCAAs, insulin secretion, beta cells proliferation, amylase, glucosidase and lipase